Saturday, 30 November 2019

Recurrent Pregnancy loss -Role of chromosomes.

Recurrent pregnancy loss (RPL) is a devastating reproductive problem affecting approximately 5% of couples trying to conceive. Genetic factors are reviewed in terms of random numerical chromosome errors in miscarriage specimens and carriers of structural chromosome rearrangements that may result in unbalanced chromosome errors in pregnancies.

In 1975, Boue et al reported that 60% of miscarriages were due to numeric cytogenetic abnormalities, specifically aneuploidies or polyploidies, based on cytogenetic analyses of 1500 miscarriages. They proposed that miscarriage occurred on the basis of natural selection; pregnancies with numeric cytogenetic abnormalities were generally not compatible with life, and therefore ended in miscarriage. Edmonds et al and Wilcox et al, estimated that 30 to 50% of all pregnancies are lost prior to 6 weeks gestation, and of these, 70% are due to numeric cytogenetic errors..

Pregnancy demise between 6 and 10 weeks of gestation occurs in approximately 15% of clinical pregnancies, of which 50% are due to numeric cytogenetic errors. After 10 weeks of gestation, pregnancy loss is infrequent, estimated at approximately 2 to 3%, of which only 5 to 6% are due to numeric cytogenetic errors. Only 0.6% of term deliveries will have a cytogenetic abnormality, most often trisomy 21, 18, or 13, or a sex chromosome aneuploidy

, genetic factors have been reviewed in terms of random numerical chromosome errors in miscarriage specimens and carriers of structural chromosome rearrangements that may result in unbalanced chromosome errors in pregnancies.

What is skewed X-chromosome inactivation?? Ans:- Recently, research has generated interest in genetic markers for recurrent loss such as skewed X-chromosome inactivation and human leukocyte antigen-G polymorphisms. Assisted reproductive technologies (specifically, preimplantation genetic diagnosis) have been offered to couples with recurrent pregnancy loss; however, more data need to be evaluated before routine use can be advocated. Management of genetic factors in RPL should include therapy based on the highest level of evidence, genetic counseling, and close monitoring of subsequent pregnancies.

genetic diagnosis

Recurrent pregnancy loss, a devastating reproductive problem, affects approximately 5% of couples trying to conceive. Although much research has sought to determine causation, just a handful of factors have been found to be associated with this reproductive disorder.

Observations on the inefficiency of reproduction prompted researchers to assess the cytogenetics of miscarriages.

Additional epidemiological studies have confirmed the original work of Boue et al .Based on the pioneering works of Edmonds et al[and Wilcox et al. it is estimated that 30 to 50% of all pregnancies are lost prior to 6 weeks gestation, and of these, 70% are due to numeric cytogenetic errors. Pregnancy demise between 6 and 10 weeks of gestation occurs in approximately 15% of clinical pregnancies, of which 50% are due to numeric cytogenetic errors. After 10 weeks of gestation, pregnancy loss is infrequent, estimated at approximately 2 to 3%, of which only 5 to 6% are due to numeric cytogenetic errors. Only 0.6% of term deliveries will have a cytogenetic abnormality, most often trisomy 21, 18, or 13, or a sex chromosome aneuploidy

These statistics are based on studies in the general reproductive population. Human reproduction appears to be an inefficient process due to errors in meiosis or somatic mitosis, which result in a nonviable pregnancy loss due to a cytogenetic abnormality. Whether the frequency of miscarriages with cytogenetic abnormalities is similar or increased in couples with recurrent pregnancy loss remains unanswered at this time. If the risk of recurrence is increased, a role for preimplantation genetic diagnosis may exist. Conversely, if the risk of recurrence is similar to that of the general reproductive population, such technology would be ineffective in improving the live birth rate in couples with reproductive loss.

Numeric and structural cytogenetic errors seen in miscarriages from couples with a history of recurrent pregnancy loss. In addition, literature on pregnancy outcome of translocation carriers, ascertained on the basis of recurrent pregnancy loss, suggest such disorder. highlighted, along with its limitations. Some of the recent molecular genetic research in the field, such as X-chromosome inactivation and human leukocyte antigen-G (HLA-G) polymorphisms, Given that preimplantation genetic diagnosis is presently being offered in some centers for treatment of recurrent pregnancy loss.

Recurrent early pregancy loss is mostly due to chromosomal disorders.

RPL : Q What % of conception proceed to live birth? Ans: Human reproduction is remarkably inefficient; nearly 70% of human conceptions do not survive to live birth.

What is the commonest cause of spont abortion?? Ans;- the most common cause for spontaneous loss, is fetal aneuploidy is particularly in the first trimester of pregnancy. Although losses may be due to A) owing to de novo fetal aneuploidy occur at similar frequencies among women with sporadic and recurrent losses, B) Equal no have couples additional associated genetic factors and C) The other causes of RSL /RPL are monogenetic etiologies.

Q, How useful is Genetic testing of the products of conception from couples experiencing two or more losses?? Ans:-Genetic testing of the products of conception from couples experiencing two or more losses may aid in defining the underlying etiology and in counseling patients about prognosis in a subsequent pregnancy.

How important is Parental karyotyping of couples Ans:-Parental karyotyping of couples who have experienced recurrent pregnancy loss (RPL) will detect some couples with an increased likelihood of recurrent fetal aneuploidy; this may direct interventions.

How important is PGS?? The utility of Perimplantation genetic analysis in couples with RPL is unproven, but new approaches to this testing show great promise.

The haemoglobin level alone can never be the sole criterion for a donor blood transfusion

In modern obstetrics bold transfusions should be the exception rather than the rule. Avoid Blood transfusion as far as possible. The haemoglobin level alone can never be the sole criterion for a donor blood transfusion .How best we, at 2019, can prevent or at least minimize pregnancy associated bood transfusion over phone to residents on emergency basis?

The main principle (mantra) are as follows which every obstetrician have to follow:-1) “Ask yourself “Is blood transfusion is absolutely essential” ?? Or else some alternative form fluid therapy will suffice?? The non selective and indiscriminate administration of blood products must be avoided at all times and 2) the indications of Blood Transfusions are a) Severe anaemia during pregnancy and b) in the postpartum period can necessitate the use of blood transfusions / plasma products and volume expanders in cases of traumatic or atonic PPH .3) If no alternative fluid do not work:-. the administration of donor blood and /or plasma products is indicted ONLY if it is proven that the products in questions have been safely manufactured and tested and if their use can avert a life threatening situation for the patient and the condition is so grave that there needs to be a sufficiently high likelihood that maternal death and morbidity cannot be averted through the use of equivalent alternatives. The non selective and indiscriminate administration of blood products must be avoided at all times. According to the literature the rate of donor blood transfusions at specialist treatment centres is 1-2%.. In our experience the critical haemoglobin level provided that the circulation is stable is approximately 6.0 g/dL . We must remember that in case of acute blood loss start giving oxygen and volume expanders immediately and let us all believe that blood transfusions represent only one of many options .The use of blood products is that they represent only one of many options in the management of the patient.

How to manage then without Blood ?? . In our experience the critical haemoglobin level provided that the circulation is stable is approximately 6.0g/dL .In case of acute blood loss start giving oxygen and volume expanders immediately. In the postpartum period can necessitate the use of blood transfusions plasma products and volume expanders. The primary principle in managing an acute severe hemorrhage is the replacement of fluids to maintain organ perfusion. Other measures include keeping to a minimum the number of blood samples taken for testing and use of the best surgical and anaesthesiological techniques to minimise blood loss.

Other obstetric Measures.

With the advent of alternative measures to control PPH by catheter balloon Tapmonade, now it must be our dedicated approach to control bleeding (PPH) by some other methods rather than blood Transfusions. There it is conveyed to the audience that in deciding for or against a blood transfusion or

Summary of the key principles for the use of blood transfusions in obstetrics.

Pregancy anaemia (including mild forms) &in gynecological cases preoperatively should be treated promptly to avoid the need for later donor blood transfusions .In general blood losses should be minimized and we must remember that the haemoglobin level alone can never be the sole criterion for a donor blood transfusion . Key factors include clinical finding the haemorrhage situation and the probability of averting significant morbidity or even death.

The decision to give a bold transfusion should be made according to the relevant guidelines.

Transfusion risks should be weighed up when making the decision

The patient’s wishes must be taken into account if at all possible

Trained staff should carry out and monitor the transfusion

The indications for and circumstances of a blood transfusion must be recorded as must any complication

Effects of iron deficiency on pregnancy

Iron deficiency adversely affects iron dependent enzymes in each cell and has profound effects on muscles and neurotransmitter activity

Iron deficiency is associated with low birthweight and preterm delivery and there is also an association with increased bold loss at delivery

Management

ABC of Oral Fe therapy in Pregnancy:-The rationale for routine supplementation with oral iron is that the increased iron demand during pregnancy cannot be met by increased absorption alone and that a high proportion of women in their reproductive years lack storage iron. Iron supplements prevent iron deficiency anaemia. Many argue that the best approach to iron deficiency in pregnancy is prevention .The world Health organization in conjunction with the International Nutritional Anemia Consultative Group and the United Nations Children’s Fund have issued guidelines recommending routine supplements

The standard oral preparations are combined with folic acid and are suitable for both prevention and treatment of iron deficiency in pregnancy, .Iron absorption from the small intestine is enhanced by ascorbic acid meat and alcohol Inhibitors to absorption include physic acid and tannins present in tea coffee and chocolate. The incidence of gastrointestinal side effects is directly related to the dose of iron taken. A dose of 60mg/day of iron may be sufficient for prophylaxis. Therefore women who have troublesome side effects may be advised to take alternate day twice weekly or weekly supplements rather than to discontinue them. For those women who are unable to tolerate oral preparations parenteral therapy with intravenous iron preparations is an alternative. This is safe in pregnancy and does not have the gastrointestinal side effects. Parenteral iron may provide a more rapid and complete correction of iron deficiency.

What is the possible maximum rise in Hb % if other conditions are optimal?? Iron deficiency diagnosed late in pregnancy may necessitate blood transfusion as the maximum rise in haemoglobin achievable with either oral or parenteral iron is 0.8g/ dL/wk.

Similar arguments apply to routine folate supplementation in pregnancy . Since a normal diet is not sufficient to meet the increased requirement for folate in pregnancy.

Prophylaxis of Fe def anemia: How & when to initiate Fe suppl?? ?? All women planning a pregnancy are advised to take 400 ug/day folate for 12 weeks pre pregnancy and or the first trimester to reduce the risk of neural tube defects and other fetal abnormalities.

Anemia in Pregnancy:-What are the indications when we should seriously consider higher dose of Folic Acid?? What are rational indications for higher dose of Folic acid? Preconception supplementation as is recommended internationally is usably 0.4 mg OD but in our country 0.4 mg(400 mcg) is not available. As we all prescribe L-M foliate .But earlier say 8 yrs back Folic acid 5 mg was the convention (three times the usual dose);with a higher dose of 5mg/day dose include women 1) Who themselves have spina bifida 2) With a previous fetus with a neural tube defect 3) Taking AEDs or sulfasalazine 4) With diabetes or obesity 5)With haemolytic SCD and other anaemias 6) Known malabsorption syndrome 7) Proven folate deficiency

Vitamin B 12 injections may be safely continued in pregnancy

Anaemia –points to remember in Exam at least :-Changes in hemodynamic:-

The plasma volume increased by 50% in pregnancy and 2) so there is a fall in haemoglobin concentration 3) Pregnancy causes a two to threefold increase in the requirement for iron and a 10to 20 fold increase in folic acid requirements. 4) Many women develop iron deficiency anaemia because they enter pregnancy with depleted iron stores. 5) may have low Ferritin:-as there are many A woman may be iron deficient despite having a normal haemoglobin level and MCV . 6) those who are planning for preg-it is better and prudent to initiate replacement by suppl of iron and folic ACID deficiency in pregnancy is prevention with oral iron and folate supplements at least in those at high risk of becoming anaemic . The maximum rise in haemoglobin achievable with either oral or parenteral iron is 0.8g/dL/wk.All women planning a pregnancy should be advised to take 0.4 mg/day folate preconception as prophylaxis against neural tube defects and other fetal abnormalities.

Flow chart if pt can’t afford too much money at a time: Or has happens at Ante OPD when too many ANC reports daily and Govt can’t afford for such reagents & Pathologists too. :-Phase wise tests of anemia :- MCV<80FL
Check Ferritin and exclude haemoglobinopathies

B) If MCV>100 Low B 12: Br careful to treat for B 12 deficinecy : recheck at post natal follow up
Check B 1 2 and folate consider LFT s+TFT Folate 5mg od FBC monthly
Iron supplements if indicated
Check reticulocytes and direct Coombs Hematology referral if abnormal
normal B 12

· \

Anaemic blood test :

Hb<11g/dL at 12 weeks

Hb<10.5 g/dL at 28 weeks

MCV<80FL

MCV80-100

Check Ferritin and exclude haemoglobinopathies

MCV>100	LowB12
	Alert GP for B12 recheck at post natal follow up

Check B12 and folate consider LFT s+TFT Folate 5mg od FBC monthly

Iron supplements if indicated

Check reticulocytes and direct coombs Haematology referral if abnormal

normalB12

B) Macrocytes:-- High MCV:-If MCV>100 and Low B 12
Investigate for for B 12 recheck at post natal follow up
Check B 1 2 and folate consider LFT s+TFT Folate 5 mg od FBC monthly, Iron supplements if indicated
Check reticulocytes and direct Coombs Hematology referral if abnormal
normal B 12

A) MCV>100 Low B 12::
Be alert for B 12 recheck at post natal follow up
Check B 1 2 and folate consider LFT +TFT, Folate 5mg od, FBC monthly
Iron supplements if indicated
Check reticulocytes and direct Coombs Hematology referral if abnormal
normal B 12

Physiology of haemopoietic system in pregancy:- 1) Physiological Increase in plasma volume is relatively greater than of red cell mass and this dilution effect increases with advancing gestation

But one should not be taken granted that all anemia’s are delusional anemias . There can be already preexisting pathological anaemia and this should not be overlooked . A significant anaemia particularly at booking is less likely to be physiological and other causes should be sought.

Erythrocyte size should be checked (microcytic, Macrocytic or Normocytic).

Thalassaemia/sickle cell disease should be managed jointly with a hematologist and offered prenatal diagnostic testing and if husband too is a trait then prenatal diagnostic is most important .

Chronic disease or malnutrition may lead to an iron deficiency and is often missed.

. Effective antenatal treatment also reduces the need for peripartum blood transfusion .

Antenatal management

Other points to remember while in practice: A) it is true that -Pregnant women obtain virtually all necessary vitamins and minerals from a healthy balanced diet- except folic acid and for some iron but hunger burden in India is too high to accept this philosophy that all is well.. B) A caveat; Anaemia in Pregnancy period quite often remain undiagnosed (Idiopathic anemia) :-Science till date is in dark about why some women develop iron deficiency even with good diet.

C ) Oral iron can be unpleasant to take with GI side effects try different formulation such as syrups It can take weeks or months to correct iron deficiency therefore treatment should be started as soon as the diagnosis is made. Appropriate iron supplementation reduces the incidence of anaemia in pregnancy by about 40%but not all. We should communicate that there are iron absorption inhibitors / Iron absorption promoters in the duodenum,. & how many of us request the concerned woman request 1) not to take PPI ( which decreases HCL) & how many clinicians ask for chewing Vit C tab prior to principal meals food. How mangos we ask them to consume iron Prepn 2 hrs before food to ensure high acid

Parenteral irons are effective when oral preparations are not tolerated advises facilities for cardiopulmonary resuscitation should be available when giving IV treatment –small incidence of anaphylaxis

Per partum management

Women giving birth with significant iron deficient anaemia are at increased risk of adverse obstetric outcomes

The non selective and indiscriminate administration of blood products must be avoided at all times. According to the literature the rate of donor blood transfusions at specialist treatment centres is 1-2%. At the Zurich University Hospital‘s obstetrics clinic the current rate is 0.5-1%

Situation that can lead to a donor blood transfusion

Postpartum anaemia with signs of shock

Severe acute blood loss following spontaneous delivery or caesarean section

Severe anaemia during pregnancy associated with maternal decompensation .Obstetric clinics and specialists should therefore be prepared for emergency blood transfusion. The availability of refrigerated blood and plasma products is essential.

But we must be aware that it is important to have strict criteria for or against the administration of blood replacement products and to be aware of the potentials and risks of these substances.

In the absence of haemoglobinopathies B12 and folate deficiencies should be excluded and iron deficiency assessed

Treat anaemia in pregnancy it is associated with an increase in adverse obstetric events including PPH and infection

FISH as a new technology for o last three decades as become an important too for chromosome analysis

For any foetal problem be it anatomic / genetic such abnormalities are usually but not always it is reflected on NT changes . Why it happens is unclear. As gestation changes - NT varies as per CRL. .If the risk calculation (statistical risk probability) is above 1: 50 then only CVS procedure for confirmation.

Risk stratification: We always are concerned about probability of chromosomal abnormality in any foetus ? If mother has one child with Down’s syndrome, than recurrent risk will be 2%. . The chromosome analysis can be done either by 1) cell culture ( traditional karyotyping) or by more recently FISH method ( Fluorescent In situ Hybridization).. In FISH method Fluorescent probe is used on the nuclei of amniocytes one signal means that the said nucleus is having monosomy ( Fluorescent probe), two signals means euploid nucleus and if some nuclei reveals three florescent signals it applies trisomy..

FISH:- Usually there are five DNA probes(probes with Fluoro Chrome) are used like 1) LS-1--21, 2) CEP-18, 3) LS-1-13 4 & 5 ) CEP- two Sex chromatins , The cells which shows two different signals after FISH procedure means normal cells i. e diploid chromosome with no alteration in number or decrease in number.& 5) Usually five chromosomes are studied in nuclei of amniocytes .like 21, 13, 18 and two sex chromosomes. This tets of FISH may occasionally exhibit trisomy or monosomy.

Normally NT steadily increase for the period foetal CRL from 44 mm to 85 mm .What is normal NT(subcutaneous fluid collection behind the nape of the neck?? The fluid thickness is for a CRL of 45 mm ( means 11 weeks ) will be 1.9 mm in 85 percentile and 50 percentile NT will be & NT will in 85 mm ( CRL at 13.6 ) but it will be 2.8 mm in 95 percentile

The nuchal translucency has to be differentiated from with cystic hygroma which are two dilated Inguinal lymphatic sac or Tr scar it the level of neck which is septate for NT .

High resolution scan is warranted. Search not only NT but also anatomic defect & cardiac defect. If NT is high along with then no foetal anatomical defect ( cardiac defect then go for CVS

The NT is only reliable from 45 - 84 mm caliper of USG should be able to read upto 0.1 mm.

Sonoembryology:_---A) UPT will be + 13 day after ovulation dose (trigger) but B) in blood earlier (RIA method ) + 9 days after ovulation .Therefore estimation hCG 5 days after test ovulation done of hcg . Average of 3 CRL measurements sac ( GDS)

Menstrual week

4^th M . Week = 2 mm sac

5thM. Week = 5mm sac

6^th M. week = 10 mm sac

7^th M. week = 20 mm sac

8 th M. week = 25mm sac

Vaginally USG:-- sac is visible when serum beta HCG is > 1500 to 1000 . But in abd USG(TAS) sac is visible when hCG is > 3000. But usually at 5^th Weeks = SAC is visible almost always. By the end of 6th weeks = Y. sac and cardiac activity seen .At 8^th weeks limb buds are usually seen.

Biochemical pregancy?? :- When two hcg values are greater than 10 IU/ lit then at this juncture if sac is not visible - then it is called “Biochemical Pregnancy”.

Average 5 days + possible even in first trimester usg

Clinical preg = Sac visible

hCG at missed dose ?

At the time of missed period (expected day of cycle, hcg in blood will be 100miu/ ml

16-23 day= 10-30 IU

24-30 days = 30-100 IU

31-38 days = 10,000 to 16000 IU

Day 35- day 45 = 200-4000 IU

2-3 mm =12000-200,000 IU

12weeks = 10,000 IU

Second Tri = 24000 – 55000 IU

3^rd Trimester 6000-48000 IU

Viability Scan :-

1) Blighted ovum - GSD > 8mm but there is no Y sac in the USG . 2) Anembryonic pregnancy. GSD > 16 mm , no foetal . p. signs of failing IUP, ) bradycardia in relation to CRL , MSD , CRL is < 5mm I e oligomaniotic sac , Poor sac growth profile , large Y. sac > 5.6 mm prior to 10 weeks / abnormal Y. sac , disappearance of CL

Normally rise of beta hCG is > 1.24 times , > 1.53, times , >1.88 times & > 2.33 times in 24 h , 48 h , 72 h & 96 hours but in ectopic there will be only 20% rise of B hCG . If no intra uterine preg is visible preg then possibilities are a) EP b) missed abortion c) failing IUP or d) self resolution of EP

Always perform USG if B hCG is above 1500 . If at such beta HCG( above 1500) sac is demonstrated at USG then in all fairness it is =normal pregancy, no sac either medical treatment MTX or better RPT b hCG after 48 hours prog is less than 10 . In abdominal USG sac should be visible when HCG level will be increases 6500 IU/ lit or

In normal pregancy the rise of b hCG will be > 55% by 48 hours & at least > 88 % by 72 hours

Friday, 29 November 2019

Pulmonary embolism

What an practising Obstetrician should know on Thromboembolism??

Point 1:-DVT remains a leading cause of obstetric morbidity and mortality.

. Point 2:- It is the hypercoagulable nature of pregnancy is the prime cause: of DVT & PE . Point 3 The hypercoagulable nature of pregnancy It remains more common in the postpartum period than during pregnancy. It is now recognized that a significant portion of these thrombotic events occur as early as the first trimester, it is prudent to start treatment soon after the pregnancy is recognized and viability confirmed, and continue until 6 weeks post delivery.

. Point 4 Why DVT is more common in Pregancy?? The increased prevalence is due to arterio of equilibrium or balance of procoagulant and anticoagulant factors in the circulation pendulum favoring toward clot formation during pregnancy. Under normal circumstances, the increased levels of clotting factors do not result in thrombus formation, but some clinical situations such as trauma or vascular injury may predispose toward lower extremity clotting. Point 5 :- Other risk factors for thrombosis during pregnancy include venous status, inactivity, obesity, prior thrombosis, antiphospholipid syndrome and thrombophilias such as factor V Leiden mutation.

It is estimated that the risk of venous thrombosis is approximately five times higher during pregnancy than in the nonpregnant state due to the hypercoagulable nature of pregnancy. While previously thought to be more prevalent in the third trimester, it is now recognized to occur at similar frequencies throughout pregnancy. Point: 6:- Despite its risk, thromboembolism during pregnancy is a poorly studied area and significant controversy remains over the management of pregnant women at risk for this disorder.

current pregnancy	control) for 5-10 days, followed by q 8-12 h injections to prolong midinterval aPTT 1 VS times control for remainder of the pregnancy; warfarin can be used postpartum	100 mg maximum) q 12 h; monitoring of anti-Factor Xa levels at 4-6 hours post injection
Patient who requires	Heparin q 8-12 h to prolong	1 mg/kg (up to 100 mg
long-term therapeutic	mid-interval aPTT 1 VS times	maximum) q 12 h;
anticoagulation	control	monitoring of anti-Factor Xa levels at 4-6 hours post injection
Previous DVT or PE	5000 units q 12 h first trimester	40 mg q 12 h; monitoring
before current	7500 units q 12 h second trimester	unnecessary for patients
pregnancy (prophylactic treatment)	10,000 units q 12 h third trimester; monitoring unnecessary	under 100 kg

That prophylactic anticoagulation 1) may not be necessary in some patients with a history of venous thromboembolism Significantly increases the risk of recurrence. Anticoagulant doses lower than needed to prolong the aPTT have been used unless the patient is thought to be at such increased risk that full anticoagulation is necessary. Because it is now recognized that a significant portion of these thrombotic events occur as early as the first trimester, it is prudent to start treatment soon after the pregnancy is recognized and viability confirmed, and continue until 6 weeks post delivery.

A recent study suggested that prophylactic anticoagulation may not be necessary in some patients with a history of venous thromboembolism. In this study of women with a single previous episode of thrombosis associated with a temporary risk factor (e.g., oral contraceptives, surgery, trauma), and no recognized thrombophilia, no recurrences were seen without treatment during pregnancy. However, the number of patients in this study was relatively small. Larger studies in the future may further support the idea that prophylactic treatment with anticoagulants is unnecessary for this type of patient.

Risks to the mother from heparin therapy include a rare thrombocytopenia and the possibility of heparin-induced osteoporosis. These risks are thought to be lower with the use of low molecular weight heparin. Heparin-induced thrombocytopenia occurs within the first week of treatment, so checking the platelet count 5 to 10 days after beginning therapy will provide reassurance. Up to one-third of women may demonstrate subclinical bone loss and the reversibility of this process is not assured. Significant maternal hemorrhage is a possibility in patients that are over- ant coagulated.

Special considerations

Patients with artificial heart valves are at a high risk for thromboembolism, stroke and valve failure and, therefore, must be therapeutically ant coagulated throughout pregnancy. Patients with a documented clot and also a family history of thromboembolic events should be evaluated for antithrombin-III, protein C or protein S deficiency because these traits are autosomal dominant with variable penetrance. Full-dose anticoagulation should be used when these conditions are identified. It is more difficult to diagnose protein S deficiency in pregnancy since levels normally decrease beginning in the first trimester; prophylaxis may be appropriate if protein S deficiency is suspected. Patients with a prior thromboembolic event who have been diagnosed with antiphospholipid antibody syndrome should be given heparin prophylaxis at a minimum, with consideration of full anticoagulation for those thought to be at significant risk. Screening for factor V Leiden and prothrombin mutation should not be performed in patients without a history of prior thrombosis, as patients with these mutations without prior thrombotic events do not need treatment. Patients with mutations of more than one factor (double heterozygote’s or those homozygous for mutation) are thought to be at high risk for thrombosis, and treatment is warranted.

There is concern regarding the use of epidural anesthesia during labor and delivery in patients treated with anticoagulants. Some anesthesiologists suggest avoiding regional anesthesia for 12-24 hours from the last injection of low molecular weight heparin, especially if full-dose treatment is used. Because of its more rapid disappearance, a shorter waiting time is used for patients on heparin, and these patients can receive regional anesthesia when laboratory tests confirm a normal PTT result. For this reason, switching from low molecular weight to standard heparin at 36 weeks' gestation may increase the number of patients eligible for regional anesthesia.

Pathophysiology-of thrombosis--Normal pregnancy is associated with an increase in the level or activity of many of the clotting factors in the blood. These increases provide a defense against hemorrhage after delivery, but they also contribute to thrombus formation. Once formed, portions of the clot can emblaze to the pulmonary tree, with symptoms ranging from mild hypoxia to cardiovascular collapse. With mild to moderate symp & few signs... LMWH vs Enoxaparin:- injections are also given twice daily because of the rapid metabolism. Monitoring of enoxaparin when given outside of pregnancy is thought to be unnecessary for most patients, but its pharmacokinetics in pregnancy are incompletely studied. If monitoring is to be performed, anti- factor Xa levels are followed, with the target being 0.6 to 1.0 IU/mL. Both heparin and low molecular weight heparins do not cross the placenta, but warfarin does due to its smaller size. Warfarin is contraindicated in pregnancy due to its fetopathic (toxic effects on foetus) (toxic effects on foetus) effects in the first trimester (stippled epiphyses and nasal and limb hypoplasia) and the risk of fetal bleeding complications in the second and third trimesters.

In postpartum period :-However, warfarin does not enter breast milk in sufficient quantities to anticoagulant the newborn, and is safe to use in the breastfeeding mother. For the patient needing full anticoagulation who prefers to take warfarin rather than frequent injections during the postpartum period, the INR is followed.

Prevention of thromboembolism

The use of anticoagulation to prevent thromboembolism is more controversial. Traditionally, chemoprophylaxis has been recommended to pregnant patients with a history of thrombosis with the idea that pregnancy.

What are the clinical features of DVT(Deep Venous Thrombosis)?

. Patients presenting with symmetric lower extremity swelling associated with A) pain and B) erythema should be usually be evident in DVT in big vessels like IVC.

Lab Diagnosis:- A) impedance plethysmography:-- impedance plethysmography compression ultrasonography for pregnant women as the primary tool for evaluation of clinical symptoms in the lower extremities. Use of Doppler also enables evaluation of thrombosis in the iliac veins . Ultrasonography is less sensitive for thrombosis below the knee. 3) Venography But Venography once a traditionally recognized method which was a gold standard for making the diagnosis, even in pregnancy but is performed less frequently now because of its invasive nature and its use of radiation.

. But all these modalities are less frequently today (i.e. impedance plethysmography, Venography) and people are insisting on B) serum D-dimer for PE cases mainly :--Assays for serum D-dimer are useful for detecting thrombosis outside of pregnancy because of its high negative predictive value, but of limited value in pregnancy because most women have increased levels by the second trimester. C) MRI use may become more common, especially for evaluation for pelvic vein thrombosis D)

?DVT

MRI or
venography

Symptoms and signs of PE:_The presenting signs and symptoms suggestive of pulmonary embolism include A) shortness of breath, B) chest pain, C) tachypnea, D) tachycardia and E) decreased oxygen saturation by pulse oxymeter.

Lab tets what to do?? A) Arterial blood gas to determine the presence of hypoxia and increased A-a gradient, both suggestive of an embolic event. However, this test is now recognized as having limited value in that many patients with pulmonary embolism are without this abnormality. B) Spiral CT scanning using IV contrast is now the primary diagnostic modality for non-pregnant patients in many centers; its use in pregnancy has not been evaluated, but is likely to be of similar accuracy as in the non-pregnant state. It may also be of use in identifying other thoracic conditions that may be responsible for the patient's symptoms. Fetal radiation exposure has been estimated to be less than 1 rad, and less than that associated with ventilation-perfusion scanning Ventilation- perfusion (V/Q) scanning but more than half of V/Q scans performed in pregnancy are non-diagnostic and require further imaging’s) Pulmonary angiography is the gold standard for diagnosing pulmonary embolus, but is invasive and associated with a risk of significant complications. D) . If a diagnosis of pulmonary embolism is made, a search for lower extremity thrombosis may be helpful in identifying the precipitating cause and directing therapy.

What is the basic Tr before she is shifted to a referral hospital or ICU from a different buildings? Treatment of acute thromboembolism: full anticoagulation using either intravenous heparin or subcutaneous low molecular weight heparin, and it is important to achieve therapeutic doses very early to prevent extension of clot. Later, the patient is then transitioned to either subcutaneous heparin or enoxaparin (or other forms of low molecular weight heparin) injections every 12 hours, which is continued for the remainder of the pregnancy and postpartum period to prevent recurrence. Tithe use of heparin injections requires monitoring to maintain the activated partial thromboplastin time (aPTT) at least 1.5 times control throughout the dosing interval. the more rapid metabolism of heparin during pregnancy, it is usually difficult to achieve prolongation of the aPTT throughout the dosing interval without an excessive peak level, even when administered three times a day.

Condition	Heparin	Enoxaparin
DVT or PE during	IV heparin (aPTT 2-3 times	Enoxaparin 1 mg/kg (up to
current pregnancy	control) for 5-10 days, followed by q 8-12 h injections to prolong midinterval aPTT 1 VS times control for remainder of the pregnancy; warfarin can be used postpartum	100 mg maximum) q 12 h; monitoring of anti-Factor Xa levels at 4-6 hours post injection
Patient who requires	Heparin q 8-12 h to prolong	1 mg/kg (up to 100 mg
long-term therapeutic	mid-interval aPTT 1 VS times	maximum) q 12 h;
anticoagulation	control	monitoring of anti-Factor Xa levels at 4-6 hours post injection
Previous DVT or PE	5000 units q 12 h first trimester	40 mg q 12 h; monitoring
before current	7500 units q 12 h second trimester	unnecessary for patients
pregnancy (prophylactic treatment)	10,000 units q 12 h third trimester; monitoring unnecessary	under 100 kg

Special considerations